Abstract
Streptozotocin (STZ) is widely used to induce diabetic rodent models. It is specifically toxic to pancreatic beta cells and causes severe destruction and dysfunction. We investigated the effect of 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG) on an STZ-induced diabetic mouse model. PLAG attenuated the glucose increase and maintained serum insulin at levels similar to those seen with control mice. In pancreatic beta cell line INS-1, STZ-induced cell apoptosis and intracellular reactive oxygen species (ROS) generation were significantly reduced to nearly normal levels after PLAG treatment. Glucose transporter 2 (GLUT2) localization analyses and glucose uptake assays showed that PLAG accelerated GLUT2 internalization, which ameliorated excessive entry of glucose, as well as STZ. STZ-induced cytotoxic effects were significantly reduced in PLAG-treated groups. The biological activity of PLAG was further confirmed in GLUT2-silenced cells, and the specificity of PLAG was verified using its derivative 1-palmitoyl-2-linoleoyl-3-hydroxyl-rac-glycerol (PLH). Our results suggest that PLAG may be a useful agent for protecting beta cells in the setting of excessive glucose influx.
Highlights
Streptozotocin (STZ) is widely used to induce diabetic rodent models
Insulin secretion was decreased in the STZ group, but the PLAG cotreatment group results were similar to those seen with the control animals
The levels of insulin secretion in the PLAG posttreatment group were similar to those seen with the control animals, even though PLAG was given beginning on day 1 when the blood glucose level was already increased by STZ treatment
Summary
Streptozotocin (STZ) is widely used to induce diabetic rodent models. It is toxic to pancreatic beta cells and causes severe destruction and dysfunction. We investigated the effect of 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG) on an STZ-induced diabetic mouse model. STZ has specific toxic effects on insulin-releasing pancreatic beta cells, making it a useful diabetogenic agent in various rodent models [2]. Several recent studies suggested that N-linked glycosylation of GLUT2 is the cause of cell surface level reduction [25] and that GLUT2 endocytosis occurs at high extracellular glucose concentrations [26] Another group found that the endosomal protein Wiskott-Aldrich syndrome homologue (WASH) regulates GLUT2 trafficking and glucose homeostasis in pancreatic beta cells [27]. PLAG has a protective effect by promoting GLUT2 intracellular trafficking, which helps attenuate ROS generation and decrease cell apoptosis in an STZ-induced diabetic model
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call